First Author | Malaterre J | Year | 2007 |
Journal | Proc Natl Acad Sci U S A | Volume | 104 |
Issue | 10 | Pages | 3829-34 |
PubMed ID | 17360438 | Mgi Jnum | J:120056 |
Mgi Id | MGI:3703812 | Doi | 10.1073/pnas.0610055104 |
Citation | Malaterre J, et al. (2007) c-Myb is required for progenitor cell homeostasis in colonic crypts. Proc Natl Acad Sci U S A 104(10):3829-34 |
abstractText | The colonic crypt is the functional unit of the colon mucosa with a central role in ion and water reabsorption. Under steady-state conditions, the distal colonic crypt harbors a single stem cell at its base that gives rise to highly proliferative progenitor cells that differentiate into columnar, goblet, and endocrine cells. The role of c-Myb in crypt homeostasis has not been elucidated. Here we have studied three genetically distinct hypomorphic c-myb mutant mouse strains, all of which show reduced colonic crypt size. The mutations target the key domains of the transcription factor: the DNA binding, transactivation, and negative regulatory domains. In vivo proliferation and cell cycle marker studies suggest that these mice have a progenitor cell proliferation defect mediated in part by reduced Cyclin E1 expression. To independently assess the extent to which c-myb is required for colonic crypt homeostasis we also generated a novel tissue-specific mouse model to allow the deletion of c-myb in adult colon, and using these mice we show that c-Myb is required for crypt integrity, normal differentiation, and steady-state proliferation. |